Prevalence of diabetes mellitus in patients with acromegaly

Early carbohydrate metabolism disorders (ECMDs) and diabetes mellitus (DM) are frequently associated with acromegaly. We aimed to assess the prevalence of ECMDs in patients with acromegaly and to compare the results with those in adults without acromegaly using two population-based epidemiologic surveys. We evaluated 97 patients with acromegaly in several phases of their disease (mean age, 56 years and estimated duration of acromegaly, 12.5 years). An oral glucose tolerance test was done in those not yet diagnosed with DM to reveal asymptomatic DM or ECMDs (impaired glucose tolerance+impaired fasting glucose). Comparisons were made between patients with acromegaly and participants from the general adult population (n=435) and an adult population with multiple type 2 diabetes risk factors (n=314), matched for gender, age and BMI. DM was diagnosed in 51 patients with acromegaly (52.5%) and 14.3% of the general population (P<0.001). The prevalence of ECMDs was also higher in patients with acromegaly than in the general population and in the high-risk group; only 22% of patients with acromegaly were normoglycaemic. The prevalence of newly diagnosed ECMDs or DM was 1.3-1.5 times higher in patients with acromegaly compared with the high-risk group. Patients with acromegaly having ECMDs or DM were older, more obese and had longer disease duration and higher IGF1 levels (Z-score). Logistic regression showed that the severity of glucose derangement was predicted by age, BMI and IGF1 levels. In patients with acromegaly, the prevalence of DM and ECMDs considerably exceeds that of the general population and of a high-risk group, and development of DM depends on age, BMI and IGF1 levels

DIABETES MELLITUS IN NEUROENDOCRINE DISEASES

There are many endocrine diseases accompanied by development of secondary diabetes mellitus (sDM). The features of the development and course of sDM in acromegaly, Cushing’s syndrome, and growth hormone (GH) deficiency are of particular interest as the prevalence of sDM associated with these pathologies is higher than that in the population. The main risk factors for sDM in acromegaly are age, female gender, arterial hypertension, family history of type 2 DM (T2DM), acromegaly activity, and duration and certain treatment methods of acromegaly. The differences of the sDM pathogenesis from pathogenesis of T2DM in the population are due to the opposite effect of GH and insulin-like growth factor 1 on glucose metabolism as well as to effect of acromegaly treatment on the mechanisms of diabetes development. The prevalence of diabetes in patients with GH deficiency, especially against the background of GH replacement therapy, is slightly higher than that in population. However, some studies have shown that GH replacement therapy may lead to normalization of the impaired glucose metabolism. High prevalence of metabolic syndrome (43%) and visceral obesity in the GH deficiency are the causes of the development of lipotoxicity (free fatty acids excess) and insulin resistance.In Cushing’s syndrome, the prevalence of early carbohydrate metabolism disturbances may reach 70%. In Cushing’s disease, chronic glucocorticoid excess determines insulin resistance and reduces insulin secretion, which results in hyperglycaemia. Currently, the recommendations for the treatment of sDM in acromegaly, hypercortisolism, and GH deficiency are the same as for the treatment of T2DM. However, as the pathogenesis is different in sDM and T2DM, the new algorithms for the diagnosis, prevention and treatment need to be developed. Prevention and timely treatment based on pathological principals will slow down the development of micro- and macrovascular complications leading to early disability and death of patients with neuroendocrine diseases

Prevalence of neoplasms in acromegaly in the Moscow Region

Rationale: Prevalence of neoplasms in patients with acromegaly and the effects of various risk factors on their development have been insufficiently studied.Aim: To assess the prevalence of thyroid, gastric and colon neoplasms in patients with newly diagnosed acromegaly, depending on their age, gender, duration and activity of the underlying disease.Materials and methods: We retrospectively analyzed data extracted from out- and in-patient medical files of 108 patients with acromegaly (25 male, 93 female). Their median age was 50.5 [range 39.3 to 59] years, median duration of acromegaly 5 [range 2 to 10] years (starting from the first appearance of the first physique abnormalities). Thyroid ultrasound was performed in 96 patients, gastroscopy in 92, and colonoscopy in 89.Results: Benign thyroid nodules were found in 50% (48/96) of patients, malignant thyroid nodules in 6.2% (6/96). Insulinlike growth factor 1 (IGF-1) levels (calculated as a percentage above upper limit of the normal range) in patients with thyroid cancer was 2.3-fold higher than in patients without nodular thyroid disease and 2-fold higher than in patients with benign thyroid nodules (р &lt; 0.012 and p &lt; 0.03, respectively). Malignant neoplasms were more often seen in the elderly (above 60 years of age), compared to younger adults (45 to 60 years) (30.8% and 4.3% of patients, respectively, p = 0.01). Male patients had higher prevalence of thyroid cancer than female (11.1% and 5.1%, respectively). Benign gastrointestinal neoplasms were observed in 51.7% of patients (18% had gastric polyps and 37% colon polyps). Age and duration of acromegaly in patients with gastric neoplasms were higher, than in those without them (р = 0.015 and p = 0.036, respectively). Colon neoplasms consisted of hyperplastic polyps (33.7%) and colon cancer (3% of patients). Patients with colon neoplasms were 11 years older than those without it (p = 0.015).Conclusion: Gastrointestinal tract and thyroid gland should be diagnostically assessed in all patients at diagnosis of acromegaly, because of the higher risk of the neoplasms in these patients. The association of higher IGF-1 levels with thyroid cancer indicates that this factor may contribute to carcinogenesis and requires further studies

EFFICIENCY OF THE ACROMEGALIC PATIENTS’ TREATMENT WITH DIFFERENT DOSES OF SANDOSTATIN LAR IN MOSCOW REGION

Background: Somatostatin analogues therapy is an important part of the acromegalic patients’ treatment. Aim: Assessment of treatment efficiency for patients with acromegaly using different doses of somatostatin analogues. Materials and methods: The data of 128 acromegaly patients registered in Moscow Region were analyzed, 79 (61.7%) of them were treated with somatostatin analogues. The treatment was started with a dose of 20 mg. If the target levels of growth hormone (GH) and type 1 insulin-like growth factor (IGF-1) were not achieved within 6-12 months, the dose was increased to 30 mg, and then to 40 mg. If GH and IGF-1 levels fell under the target values, the dose was decreased to 10 mg. The rate of achievement of optimal GH and IGF-1 levels was analyzed depending on the somatostatin analogue doses used. Results: The percentage of the acromegalic patients who were under the first and the second lines of drug therapy, was almost similar:  55.7 and 44.3%, respectively. Sandostatin LAR in dose of 10 mg was given to 4 (5.1%) of 79 patients, 20 mg – to 33 (41.8%), 30 mg – to 11 (13.9%), and 40 mg – to 31 (39.2%) patients. The target levels of GH and IGF-1 were achieved in 57.6, 54.5, and 32.2% of patients, who received preparation in doses 20, 30, and 40 mg, respectively. Achievement of, at least, one planned criterium (GH or IGF-1) was additionally noted in 10 of 33 (30.3%), 4 of 11 (36.2%), and 9 of 31 (29%) patients within these study groups. The rate of side effects didn’t increase with the raising of оctreotide dose. Conclusion: Application of long-acting release octreotide (Sandostatin-LAR) in doses of 30 and 40 mg is safe and allows to increase percentage of acromegalic patients who achieve a biochemical control over acromegaly